A collaborative study is proposed to confirm and expand the observations of Truitt (1971), Korsten et al. (1975) and Lindros et al. (1980) of an elevated acetaldehyde (AcH) to ethanol (EtOH) ratio in the blood of drinking alcoholics using an improved HPLC method for AcH. Furthermore, this study will replicate the studies of Schuckit et al. (1979-1984) which found a similar elevation in the AcH/EtOH ratio in non-alcoholic sons of alcoholics. Subjects will be tested for their blood and breath AcH/EtOH ratios, subjective euphoria rating, neurologic test impairment and degree of facial flushing at various BAC's after readmission to the hospital for detoxification (alcoholics) of after i.v. administration of EtOH to maintain a BAC of 50-60 mg/dl for 1 hour in non-alcoholic relatives. AcH will be measured in breath and blood by a HPLC method with greater sensitivity to low levels of AcH and which also prevents artifactual in vitro non-enzymatic conversion of EtOH to AcH (Truitt and Rowe, 1983). Subjects will be recruited from 60 families with and 60 without a history of alcoholism (FHP and FHN) and several relatives from each family will be tested including at least one alcoholic member of the former group. Alleged relationships on pedigree will be verified by RBC surface antigens, serum protein electrophoresis and HLA typing. In addition, leukocyte DNA will be isolated and offered to Dr. Howard Edenberg, Indiana University, and others for identification of ADH and Ald-DH isozymes by restriction fragment length polymorphism (RFLP) using cDNA molecular probes. Alcoholic families will be recruited from patients participating in the alcoholism treatment programs at the Providence, R.I. VA Medical Center and Ignatia Hall, St. Thomas Hospital, Akron, OH. Control families will show comparable profiles of race, ethnicity, gender, ages, socio-economic status, height/weight ratio and psychiatric history. Pedigrees will be developed for both sets of families to examine the relationship between (1) the diagnosis of alcoholism, (2) subjective euphoria, facial flushing and neurologic impairment, (3) blood AcH/EtOH ratio and (4) the genotype of ADH and Ald-DH isozymes. If the FHP families can be shown to differ from the FHN by the frequency of higher blood AcH/EtOH ratios among its members, then their pedigrees will be used to examine the mode of inheritance of the phenotype. If there appears to be more than one variant, each will be characterized. This may help explain the etiology of alcoholism, aid our understanding of recidivism, provide a method of screening for predisposition to alcoholism and advance the search for the mechanism of alcoholism's genetic inheritance.